Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.

Vfend (Pfizer)

50 mg and 200 mg tablets

30 mL glass vials containing 200 mg as lyophilised powder

Approved indication: systemic fungal infections

Australian Medicines Handbook section 5.2.3

The triazole antifungal drugs, such as fluconazole and itraconazole can be used to treat systemic fungal infections. Their fungicidal activity results from the inhibition of ergosterol synthesis in the cell membrane. Voriconazole is a new triazole drug with a broad spectrum of activity. In addition to the treatment of serious fungal infections, voriconazole can be used to prevent infections in patients with febrile neutropenia.

A clinical trial randomised 837 patients with febrile neutropenia to empirical therapy with liposomal amphotericin B or voriconazole. Fungal infections occurred in 21 patients given amphotericin B and in eight patients taking voriconazole. Breakthrough infections were particularly reduced in patients with relapsed leukaemia or an allogenic transplant.1

In a study of 277 patients with invasive aspergillosis 29% of those taking voriconazole had died within 12 weeks compared with 42% of those taking amphotericin B. Voriconazole can also be used when fungal infections such as invasive candidiasis do not respond to other antifungal drugs.

A loading dose of voriconazole will produce steady-state concentrations within 24 hours rather than the six days it usually takes with twice-daily doses. The tablets are well absorbed so the loading dose can be given orally. Voriconazole is metabolised in the liver and as this metabolism becomes saturated voriconazole has non-linear pharmacokinetics. There is a lot of variability in the pharmacokinetics of voriconazole, particularly in certain ethnic groups who are poor metabolisers. As the metabolism of voriconazole involves cytochrome P450 2C9, 2C19 and 3A4 there are many potential drug interactions. Co-administration with drugs such as carbamazepine, ergotamine, pimozide and cisapride is contraindicated.

Hepatic toxicity including fatal liver failure can occur so patients need regular monitoring of liver function. A more common adverse reaction is altered vision. This affects approximately 30% of patients. They may complain of blurring, photophobia or changes in colour vision. Some will develop hallucinations. Rashes are common and some patients have developed Stevens-Johnson syndrome.

Although voriconazole has some significant adverse effects some of these, such as renal dysfunction, occurred less frequently than they did with amphotericin B. There is, however, controversy about whether voriconazole is as effective as amphotericin B. In the study of febrile neutropenia the overall treatment success rate was 26% for voriconazole and 30.6% for liposomal amphotericin B. The American Antiviral Drugs Advisory Committee recommended that the Food and Drug Administration should not approve voriconazole.2While there are problems with fluconazole and itraconazole, the role of voriconazole requires further study.

References

  1. Walsh TJ, Pappas P, Winston DJ, Lazarus HM, Petersen F, Raffalli J, et al. Voriconazole compared with liposomal amphotericin B for empirical antifungal therapy in patients with neutropenia and persistent fever. N Engl J Med 2002;346:225-34.
  2. Powers JH, Dixon CA, Goldberger MJ. Voriconazole versus liposomal amphotericin B in patients with neutropenia and persistent fever [letter]. N Engl J Med 2002;346:289-90.